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If you or your child has congenital adrenal hyperplasia (CAH), you probably already know how important hormones are. Cortisol, aldosterone, adrenocorticotropic hormone (ACTH), and androgen levels aren’t just numbers on a lab report. They often drive CAH symptoms like fatigue, early puberty, or dehydration. These hormones are all connected through an important system called the hypothalamic-pituitary-adrenal (HPA) axis.
In this article, we’ll cover what you need to know about the HPA axis and how it relates to CAH. We’ll explain how it works, how CAH can interfere with hormone balance, and what this means for treatment and long-term health.
The HPA axis is one of the body’s most important endocrine (hormone) systems. It’s a three-part chain that connects the brain to the adrenal glands, which are located above the kidneys.
“HPA” stands for “hypothalamus, pituitary gland, and adrenal glands.” The hypothalamus is an important area of the brain that regulates body functions like temperature, hunger, sleep, and mood. The pituitary and adrenal glands produce important hormones. Here’s how the HPA axis works:
This system forms a feedback loop. When cortisol levels are within a healthy range, the brain senses this and slows down CRF and ACTH production. Low cortisol levels trigger the hypothalamus and pituitary gland to release more CRF and ACTH, and hormone production by the adrenal glands is stimulated.
The main function of the HPA axis is to regulate the body’s stress response. However, it also helps regulate other bodily functions, including:
The HPA axis follows a daily rhythm, with cortisol levels normally peaking in the morning and dropping at night. Since this system influences so many body systems, even small changes along the axis can cause big effects on health, which is exactly what happens in CAH.
The HPA axis works by releasing and regulating three main types of steroid hormones: cortisol, aldosterone, and androgens. It also depends on the signaling hormones CRH and ACTH to keep the system working and balanced.
Cortisol is the body’s main stress hormone. It helps control energy, fight inflammation, and keep blood glucose (sugar) steady. Normally, cortisol sends a signal back to the brain to slow down ACTH release. This process is called negative feedback. In CAH, this step often fails because not enough cortisol is produced or the levels are too low, which disrupts the feedback loop.
Aldosterone is a mineralocorticoid. Its job is to manage the levels of potassium and salt in your blood. This keeps blood pressure normal and prevents dangerous salt loss. Without enough aldosterone, a person can develop a salt-wasting crisis. This is when the body loses so much salt that blood pressure drops to a dangerously low level. This problem is most common in classic, salt-wasting CAH, where both cortisol and aldosterone are affected.
Johns Hopkins Medicine explains that androgens are a type of sex hormone, and both males and females make them. They control growth during puberty and affect hair, skin, and fertility. In CAH, precursors — the substances the body normally uses to make cortisol — often get converted into adrenal androgens instead. This androgen overproduction leads to CAH symptoms such as irregular periods, early puberty, or virilization in females (male characteristics in girls).
In short, cortisol, aldosterone, and androgens are the outputs of the adrenal glands. The hormones involved in the HPA axis — CRF and ACTH — are the signals that drive the system.
Understanding the HPA axis helps explain the chain reaction that leads to hormone imbalances in CAH. In most people with CAH, including those with classic and nonclassic forms, there are mutations (changes) in the gene that makes the enzyme 21-hydroxylase. This is one of five enzymes the adrenal glands need to produce cortisol. Without enough 21-hydroxylase, the body doesn’t make enough cortisol.
When cortisol levels are low, the hypothalamus and pituitary gland don’t get the message to slow down CRF and ACTH production. Instead, they continue to make and release more. Higher levels of these signals drive the adrenal glands to keep making more hormones. However, since 21-hydroxylase is missing, the adrenal glands still can’t make enough cortisol.
Instead, the precursors of cortisol, such as 17-hydroxyprogesterone, get pushed into other pathways. These turn into extra androgens, leading to androgen overproduction. That’s why people with CAH often have high levels of adrenal androgens, leading to early puberty, irregular periods, or excess hair and acne.
In classic CAH — especially salt-wasting — the problem can also affect aldosterone. This can lead to low blood pressure and a salt-wasting crisis. In nonclassic CAH, cortisol and aldosterone levels may be near normal, but the HPA axis may still cause the body to make too many androgens.
In CAH, the HPA axis doesn’t just get out of balance — it gets locked into overdrive. Because cortisol levels never rise enough to quiet the system, the hypothalamus and pituitary gland keep releasing more CRH and ACTH. Over time, this constant stimulation makes the adrenal glands grow larger, a change called adrenocortical hyperplasia. This is where the name “congenital adrenal hyperplasia” comes from.
The result is a system that’s always switched on. Normally, cortisol rises in the morning to give you energy and falls at night to help you sleep. But, in people with CAH, this timing is off. This can cause fatigue and negatively affect quality of life.
Another effect of this constant drive is the buildup of hormone precursors. Because these precursors can’t flow into the cortisol pathway, they get diverted into making more adrenal androgens. This explains why excess androgens remain a problem even when aldosterone is normal. It can trigger early puberty, acne, or reduced fertility. In girls and women, this can cause symptoms like irregular periods or changes in the genitalia.
Left untreated, people with CAH are at increased risk for an adrenal crisis. This is a sudden, life-threatening condition in which the adrenal gland can’t make the cortisol needed to respond to stress or injury.
Treatment for CAH works by replacing the hormones the body can’t make on its own (replace missing cortisol and, when needed, aldosterone) and reducing high levels of androgens. By doing this, doctors aim to restore the balance in the HPA axis and stop the cycle of constant ACTH overdrive.
Glucocorticoids are a mainstay of treatment. These include synthetic forms of cortisol, such as:
These medications raise cortisol levels in the blood. However, high doses may be needed to tell the hypothalamus and pituitary gland to release less CRF and ACTH. This lowers the overstimulation of the adrenal glands. With less ACTH, androgen production also falls.
In salt-wasting forms of CAH, people may also need to take fludrocortisone. This is a mineralocorticoid that replaces aldosterone. It helps maintain blood pressure and prevents dangerous salt loss.
The challenge is often finding the right dose and timing for CAH medications. Too little glucocorticoids means cortisol stays low and ACTH remains high. Taking too much can strongly suppress the HPA axis, leading to growth issues, weight gain, or other side effects. Over time, treatments may need to be adjusted.
On CAHteam, people share their experiences with congenital adrenal hyperplasia, get advice, and find support from others who understand.
What resources have helped you better understand hormone balance in CAH? Let others know in the comments below.
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